The Vitamin D Analog Calcipotriol Combined with Aminolevulinate-Mediated Photodynamic Therapy for Human Psoriasis: A Proof-of-Principle Study

We previously showed that select agents (methotrexate or vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation play a major role, could serve as a useful model to test the effects of prodifferentiating agents upon PpIX levels in a nonneoplastic setting. In particular, vitamin D, a treatment for psoriasis that restores (i.e., increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of seven patients with bilaterally matched psoriatic plaques. A regimen in which calcipotriol 0.005?% ointment was applied for six days prior to ALA-PDT using blue light led to preferential increases in PpIX (ca. 50?%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with vitamin D and ALA-PDT for psoriasis.